Antiviral agents

Antiretroviral agents are synthetic antiviral agents that have antiviral activity against human immunodeficiency virus (HIV) and are used in the management of HIV infection. There currently are 5 different classes of antiretroviral agents commercially available: nucleoside reverse transcriptase inhibitors (NRTIs), HIV protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors, and HIV fusion inhibitors.

Ribavirin is indicated in the treatment of carefully selected hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus (RSV). In addition, ribavirin (600 to 1800 mg / day for 10 to 14 days) has shown effectiveness in acute and chronic hepatitis, herpes genitalis, measles, and Lassa fever. The antiviral mechanism of action of ribavirin relates to alteration of cellular nucleotide pools and inhibition of viral messenger RNA synthesis. Intracellular phosphorylation to the mono-, di-, and triphosphate derivatives is mediated by host cell enzymes.

Lamivudine is a nucleoside reverse transcriptase inhibitor, which inhibits replication of HIV and hepatitis B virus (HBV). HIV infection: Epivir is used in combination with other antiretroviral agents for the treatment of HIV infection.

The most common adverse effects associated with antiretroviral regimens containing etravirine are nausea and skin rash (usually mild to moderate) and generally appearing in the second week of treatment and resolving within 1 to 2 weeks. Severe skin reactions, including erythema multiforme and Stevens-Johnson syndrome, have occurred. Raised liver enzyme values, glucose levels, and serum-cholesterol and -triglyceride concentrations have been reported.

The most common adverse effects associated with antiretroviral regimens containing enfuvirtide are local injection site reactions with resultant pain, erythema, induration, nodules and cysts, pruritus, and ecchymosis. These reactions have been reported to occur in 98% of patients, but only a small minority needed to stop therapy. Other very common adverse effects include nausea, diarrhoea, weight loss, and peripheral neuropathy.

The most common adverse effects associated with antiretroviral regimens containing emtricitabine are headache, diarrhoea, and nausea; hyperpigmented skin discoloration is very common in children and common in adults. Other common adverse effects include abdominal pain, vomiting, dyspepsia, abnormal dreams, asthenia, dizziness, insomnia, pain, allergic skin reactions, pruritus, rashes, and urticaria. Abnormal laboratory test results associated with emtricitabine-containing regimens include hyperbilirubinaemia, increases in serum lipase and pancreatic amylase, and raised liver enzymes. There have also been reports of neutropenia and anaemia.

Didanosine is converted intracellularly to its active form dideoxyadenosine triphosphate. This triphosphate halts the DNA synthesis of retrovirases, including HIV, through competitive inhibition of reverse transcriptase and incorporation into viral DNA.

Delavirdine acts by non-competitive inhibition of HIV-1 reverse transcriptase; it binds to the enzyme, disrupting the conformation of its catalytic site and impairing its RNA- and DNA-dependent polymerase activity. Resistance to delavirdine and emergence of cross-resistance to other non-nucleoside reverse transcriptase inhibitors has been seen.

Darunavir is a selective inhibitor of HIV-1 protease. It interferes with the formation of essential viral proteins making them incapable of infecting other cells. Viral resistance develops rapidly when HIV-protease inhibitors are given alone and therefore they are used with other antiretrovirals.

Cidofovir undergoes intracellular phosphorylation by cellular kinases to the antiviral metabolite, cidofovir diphosphate, which acts as a competitive inhibitor of viral DNA polymerase. It is active against a range of herpesviruses including CMV, and, since its activity is not reliant on viral enzymes, may retain activity against some aciclovir- and foscarnet-resistant viruses. Cross-resistance with ganciclovir is common.